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Characterisation of the sarcoidosis-associated variant of annexin A11.

Authors: Lux, Fatimathas; Stephen E, Moss;

Characterisation of the sarcoidosis-associated variant of annexin A11.

Abstract

Recent studies on the genetic background of sarcoidosis have resulted in the discovery of a strongly associated single nucleotide polymorphism (SNP) that switches a highly conserved arginine to a cysteine at position 230 in annexin A11. The effect of the R230C SNP on the cellular distribution and Ca(2+)-sensitivity of annexin A11 was investigated through over-expression of GFP tagged annexin A11 in A431 cells. Cells were stimulated with calcium mobilizing agonists and changes in the cellular localisation of GFP tagged annexin A11 were recorded. Neither variant of annexin 11, nor any truncation mutants, exhibited any response to EGF. In addition, there was no relocalisation of the GFP tagged C-terminal annexin A11 variants in response to ionomycin. However, both the wild type and sarcoidosis associated variants of annexin A11-GFP relocalised to the plasma membrane and then the nuclear envelope in response to ionomycin. These observations show that the sensitivity of annexin A11 to a robust, sustained rise in intracellular calcium, is not significantly affected by the sarcoidosis associated SNP. This does not rule out functional affects in the extracellular milieu, in cytokinesis, nuclear envelope breakdown or in response to other intracellular signals.

Keywords

Cell Nucleus, Sarcoidosis, Sequence Homology, Amino Acid, Annexins, Green Fluorescent Proteins, Molecular Sequence Data, Molecular Conformation, Genetic Variation, Models, Biological, Polymorphism, Single Nucleotide, Protein Structure, Tertiary, Cell Line, Tumor, Mutation, Humans, Calcium, Amino Acid Sequence

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
5
Average
Average
Average
gold